Conjugation is rate limiting in hepatic transport of ursodeoxycholate in the rat

Abstract
It has been reported that biliary secretion is the limiting step in the hepatic transport of bile acids by the hepatocyte from plasma to canalicular bile. The role of conjugation in the transport process using ursodeoxycholate (UDCA) and tauroursodeoxycholate (TUDCA), 2 bile acids with low liver toxicity, was examined. Rats were given constant i.v. infusions of cholate (C), taurocholate (TC), UDCA or TUDCA at progressively increasing rates. The biliary maximum secretory rate (SRm) (in nmol .cntdot. min-1 .cntdot. 100 g body wt-1) for TC (1835.2 .+-. 135.5, mean .+-. SE) was not significantly different from that of C (1749.4 .+-. 85.6). The SRm for TUDCA (5909.4 .+-. 304.4) was .apprx. 7-fold that of UDCA (802.1 .+-. 134.2), the difference being statistically significant (P < 0.001). The SRm of UDCA in the presence of a taurine infusion (1367 .+-. 84.4) was higher than that of UDCA infused alone but still much lower than that of TUDCA, sodium phenobarbital pretreatment did not increase SRm of UDCA alone or in the presence of a taurine infusion. In the rat conjugation may be the rate-limiting step in the overall transport of UDCA (and perhaps other bile acids) by the liver and the conjugation process itself is probably limiting, rather than the availability of taurine. Although not mandatory for secretion into bile, conjugation of bile acids apparently confers a biological advantage, possibly by increasing the solubility of the bile acid.

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